Plasma High-density Lipoprotein Cholesterol Concentrations Research Articles

Role of GPR109A Receptor in the Efficacy of Nicotinic Acid

Nicotinic acid is used to treat dyslipidemia from the past few decades. Nicotinic acid has the capability to increase plasma HDL cholesterol concentration, and so it is being used as a potential pharmacological agent. Nicotinic acid has an unwanted side effect called flushing, which effect the patients compliance as this is unpleasant . With the help of receptor GPR109A for nicotinic acid it is possible to understand the underlying mechanism of action and effects of nicotinic acid, and this helped in maximizing the potential pharmacological effects of nicotinic acid and reducing the flushing side effects.GPR109A is a G protein coupled receptor which is activated by nicotinic acid (NA).The role of GPR109A receptor in the efficacy of nicotinic acid is discussed in this paper.

Novel associations between parental and newborn cord blood metabolic profiles in the Norwegian Mother, Father and Child Cohort Study

BackgroundMore than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal and paternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile.MethodsThis study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in this study consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure was used to correct for multiple testing.ResultsAmong mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoprotein cholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine, creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated (0.001 ≤ q ≤ 0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine, tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoprotein were significantly positively associated (0.02 ≤ q ≤ 0.08). Among fathers with hypercholesterolemia, paternal and newborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q = 0.04). Among fathers without hypercholesterolemia, no significant associations were found between paternal and newborn metabolites. Sex differences were found for many cord blood lipids.ConclusionsMaternal and paternal metabolites and newborn sex were associated with several cord blood metabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.

High-density lipoproteins, reverse cholesterol transport and atherogenesis.

Plasma HDL-cholesterol concentrations correlate negatively with the risk of atherosclerotic cardiovascular disease (ASCVD). According to a widely cited model, HDL elicits its atheroprotective effect through its role in reverse cholesterol transport, which comprises the efflux of cholesterol from macrophages to early forms of HDL, followed by the conversion of free cholesterol (FCh) contained in HDL into cholesteryl esters, which are hepatically extracted from the plasma by HDL receptors and transferred to the bile for intestinal excretion. Given that increasing plasma HDL-cholesterol levels by genetic approaches does not reduce the risk of ASCVD, the focus of research has shifted to HDL function, especially in the context of macrophage cholesterol efflux. In support of the reverse cholesterol transport model, several large studies have revealed an inverse correlation between macrophage cholesterol efflux to plasma HDL and ASCVD. However, other studies have cast doubt on the underlying reverse cholesterol transport mechanism: in mice and humans, the FCh contained in HDL is rapidly cleared from the plasma (within minutes), independently of esterification and HDL holoparticle uptake by the liver. Moreover, the reversibility of FCh transfer between macrophages and HDL has implicated the reverse process - that is, the transfer of FCh from HDL to macrophages - in the aetiology of increased ASCVD under conditions of very high plasma HDL-FCh concentrations.

The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study.

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.

Elevated Apolipoprotein A1 and HDL Cholesterol Associated with Age-related Macular Degeneration: 2 Population Cohorts.

To enable prevention and treatment of age-related macular degeneration (AMD), understanding risk factors for AMD is important. We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol and low levels of low-density lipoprotein (LDL) cholesterol are associated with increased risk of AMD. From the Danish general population, we studied 106 703 and 16 032 individuals in the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS) with median follow-up of 9 and 32 years, respectively.The main outcome measures were 1787 AMD in CGPS and 206 in CCHS. Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40 (95% CI: 1.20-1.63) and 1.22 (1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18 (1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L (39 mg/dL) higher HDL, and 1 mmol/L (39 mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19 (1.07-1.32), and 1.05 (1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Elevated plasma apolipoprotein A1 and HDL cholesterol and lower LDL cholesterol are associated with increased risk of AMD.

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis.

The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.

Effect of Dietary L-Methionine Supplementation on Growth Performance, Carcass Traits, and Plasma Parameters of Starter Pekin Ducks at Different Dietary Energy Levels.

Simple SummaryTremendous improvements have been made in the duck commercial industry, especially in aspects such as the increase of body weight and shortening of the production cycle. Meat duck production has been increasing annually worldwide. Improvements in precise nutrition were crucial for ducks to improve growth efficiency and reduce diet costs. Currently, L-Met, a new methionine (Met) source, has been commercially available for duck diet formulation. The bioavailability of L-Met is greater than DL-Met for growth performance in duck. The present study estimated the Met requirement of starter Pekin ducks from 1 to 21 days of age by supplementing crystal L-Met to formulate the diets at different ME levels. The results suggested that the Met requirement of starter Pekin ducks was affected by dietary ME levels. The data potentially provide theoretical support for the utilization of crystalline L-Met in duck production.A 2 × 6 factorial experiment was conducted to determine the influences of dietary metabolizable energy (ME) and methionine (Met) levels on growth performance, carcass traits, and plasma biochemical parameters of starter Pekin ducks from 1 to 21 days of age. A total of 600 one-day-old male Pekin ducklings were randomly assigned to 12 groups (six replicates each group and eight ducks per replicate) in a 2 × 6 two-factor arrangement. The basal Met levels of two basal diets (11.54 and 12.52 MJ/kg ME) were 0.31 and 0.29%, respectively. The crystalline L-Met was supplemented to yield six diets according to different supplemental levels (0, 0.05, 0.10, 0.15, 0.20, and 0.25%). The results showed that the body weight (BW) and average daily weight gain (ADG) were increased (p < 0.05) with increasing dietary Met levels. Dietary ME levels changed from 11.54 to 12.52 MJ/kg increased the BW and ADG (p < 0.05) as well as decreased the average daily feed intake and feed to gain ratio (p < 0.05). As the dietary Met level increased, leg muscle yield increased (p < 0.05). Conversely, increasing the dietary ME level decreased the leg muscle yield (p = 0.0024) and increased abdominal fat (p < 0.001). Meanwhile, the concentrations of total cholesterol (TCHO), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) in plasma were decreased (p < 0.05) when the ME levels of diets changed from 11.54 to 12.52 MJ/kg. Meanwhile, the plasma TCHO and HDLC concentrations decreased (p < 0.05) as dietary Met levels increased. Based on the linear-broken line model, the dietary Met requirement of starter Pekin ducks from 1 to 21 days of age for optimal ADG were 0.362% (0.052% supplemental L-Met) at 11.54 MJ ME/kg and 0.468% (0.178% supplemental L-Met) at 12.52 MJ ME/kg, respectively, when crystal L-Met was supplemented to formulate the diets. This suggested that the Met requirement of starter Pekin ducks was affected by dietary ME levels. The data potentially provide theoretical support for the utilization of crystalline L-Met in duck production.

The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR'3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration.

Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis, which is involved in the formation of atherosclerotic plaque. This study aimed to evaluate whether LDLR gene polymorphisms are significantly associated with ACS and the plasma lipids profile. Three LDLR gene polymorphisms located in the UTR′3 region (c.*52 A/G, c.*504 A/G, and c.* 773 A/G) were determined using TaqMan genotyping assays in a group of 618 ACS patients and 666 healthy controls. Plasma lipids profile concentrations were determined by enzymatic/colorimetric assays. Under co-dominant and recessive models, the c.*52 A allele of the c.*52 A/G polymorphism was associated with a higher risk of ACS (OR = 2.02, pCCo-dom = 0.033, and OR = 2.00, pCRes = 0.009, respectively). In the same way, under co-dominant and recessive models, the c.*773 G allele of the c.*773 A/G polymorphism was associated with a high risk of ACS (OR = 2.04, pCCo-dom = 0.027, and OR = 2.01, pCRes = 0.007, respectively). The “AAG” haplotype was associated with a high risk of ACS (OR = 1.22, pC = 0.016). The c.*52 AA genotype showed a lower HDL-C concentration than individuals with the GG genotype. In addition, carriers of c.*773 GG genotype carriers had a lower concentration of the high-density lipoprotein-cholesterol (HDL-C) than subjects with the AA genotype. Our data suggest the association of the LDLR c.*773 A/G and LDLR c.*52 A/G polymorphisms with both the risk of developing ACS and with a lower concentration of HDL-C in the study population.

The Alcohol-High-Density Lipoprotein Athero-Protective Axis.

Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. More recent evidence has accrued against the hypothesis that raising plasma HDL concentrations prevents ASCVD so that other metabolic processes associated with alcohol consumption have been considered. This review explored the roles of other metabolites induced by alcohol consumption—triglyceride-rich lipoproteins, non-esterified free fatty acids, and acetate, the terminal alcohol metabolite in athero-protection: Current evidence suggests that acetate has a key role in athero-protection but additional studies are needed.

Physical Exercise May Increase Plasma Concentration of High-Density Lipoprotein-Cholesterol in Patients With Alzheimer's Disease.

Lifestyle factors have been shown to increase the risk of developing Alzheimer’s disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein–cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n = 90) or treatment as usual (n = 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the “high exercise sub-group” compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars.

OBJECTIVEDebate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males.RESEARCH DESIGN AND METHODSSixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and whole-body metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers.RESULTSConsumption of the SFA diet significantly increased IHTAG by mean ± SEM 39.0 ± 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P < 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting β-hydroxybutyrate plasma concentrations.CONCLUSIONSConsumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.

Myocardial Changes in Diabetic and Nondiabetic Nonhuman Primates.

Diabetic human patients have increased risk of heart failure compared to healthy subjects. The underlying mechanisms for this are not fully understood, and to help develop improved treatment strategies, well-characterized animal models are essential. To investigate cardiac dysfunction in diabetes, this study evaluated myocardial changes in 10 aging rhesus monkeys with and without diabetes. Based on evaluation of plasma glycosylated hemoglobin and glucose, 7 of 10 rhesus macaques had diabetes for a minimum of 11 months, while 3 of 10 were categorized as nondiabetic. A detailed histological examination of formalin-fixed left ventricular myocardial samples was followed by a semiquantitative evaluation of myocardial fibrosis and fat infiltration; digital quantifications of myocardial collagen, lipofuscin, and nuclear area fractions; and measurements of cardiomyocyte diameter. Histological myocardial evaluation revealed the presence of lipofuscin; large nuclei; interstitial, replacement, and vascular fibrosis; adipocyte infiltration; and vacuolar degeneration with atrophy of cardiomyocytes and fibrosis. However, there were no differences between groups for semiquantitative fat infiltration, fibrosis, cardiomyocyte size, collagen, or nuclear and lipofuscin area fraction. Lipofuscin area fraction correlated with plasma insulin, triglyceride, total cholesterol, and high-density lipoprotein cholesterol concentrations. In conclusion, myocardial pathological changes were found in left ventricular myocardium in aged rhesus macaques, independent of the stage of diabetes. The duration of diabetes might have been too short to cause differences between groups.

The Correlation between Blood HbA1c and HDL Subclasses in Patients with Metabolic Syndrome.

Metabolic syndrome (MS) is characterized by a constellation of metabolic disorders. Hyperglycemia and dyslipidemia are the major risk factors of MS. Here we performed a study to explore the association between glycated hemoglobin A1c (HbA1c) and high-density lipoprotein (HDL) subclasses in patients with MS. We included 101 MS patients and 77 healthy subjects in this study. Blood tests were executed to assess the blood glucose and lipid indicators, including HbA1c, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B100 (apoB100), preβ1-HDL, HDL3b, apoB100/AI, apolipoprotein AI (apoAI), HDL2b and HDL2a. Multivariate linear regression was used to explore potential relationship between HDL subclasses and HbA1c. Compared with control group, the levels of HbA1c, FPG, TG, TC, LDL-C, apoB100, preβ1-HDL, HDL3b, apoB100/AI and LDL-C/HDL-C were significantly increased in MS subjects (p < 0.01), while plasma concentrations of HDL-C, apoAI, HDL2b and HDL2a were significantly decreased in MS subjects (p < 0.01). With the increase of whole blood HbA1c levels in MS subjects, preβ1-HDL was elevated gradually, while HDL2a was decreased gradually. Blood HbA1c level is associated with the changes in HDL subclass distribution in patients with MS.

Copper bioavailability, mineral utilization, and lipid metabolism in broilers

The study was conducted to investigate the effects of copper (Cu) sources and levels on mineral utilization, tissue copper residues, and lipid metabolism in Arbor Acres broilers. A total of 640 male broilers were randomly divided into 5 groups with 8 replicates per group and 16 broilers per replicate. The experiment was used in a 2 × 2 + 1 factorial experiment design. Broilers in the control group were fed a basal diet, and animals in the other four groups were fed basal diets supplemented with Cu from copper sulphate and copper methionine. Copper concentrations of the experimental diets were 20 and 40 mg Cu/kg dry matter. A metabolism trial of 4 days was conducted during the last week of experimental feeding. Neither Cu source nor Cu level affected average daily gain, average daily feed intake or feed gain ratio (P &amp;gt; 0.05). Broilers fed 40 mg Cu/kg diets had lower plasma cholesterol than those in the control group (P &amp;lt; 0.05). Copper supplementation decreased (P &amp;lt; 0.05) plasma low-density lipoprotein cholesterol but did not alter plasma high-density lipoprotein cholesterol concentrations or plasma triglyceride concentrations. Copper sulphate supplementation increased (P &amp;lt; 0.05) liver Cu but did not alter pectorals Cu, heart Cu, tibia Cu and tibia P. Broilers fed 40 mg/kg Cu from copper sulphate had a lower (P &amp;lt; 0.05) tibia Ca level. The concentration of liver Cu in the broilers fed copper methionine diets was higher (P &amp;lt; 0.05) than that in those fed copper sulphate. Compared with copper sulphate (100%), the relative bioavailability value of copper methionine was 117%. In conclusion, the relative bioavailability of copper methionine obtained in this study was greater than that of copper sulphate. Copper plays an important role in plasma lipids and in the digestion of dietary Ca in broiler chickens.

Urinary Ethyl Glucuronide Can Be Used as a Biomarker of Habitual Alcohol Consumption in the General Population

ABSTRACTBackgroundAlcohol consumption is a frequently studied risk factor for chronic diseases, but many studies are hampered by self-report of alcohol consumption. The urinary metabolite ethyl glucuronide (EtG), reflecting alcohol consumption during the past 72 h, is a promising objective marker, but population data are lacking.ObjectiveThe objective of this study was to assess the reliability of EtG as a marker for habitual alcohol consumption compared with self-report and other biomarkers in the general population.MethodsAmong 6211 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, EtG concentrations were measured in 24-h urine samples. EtG was considered positive when concentrations were ≥100 ng/mL. Habitual alcohol consumption was self-reported by questionnaire (categories: no/almost never, 1–4 units per month, 2–7 units per week, 1–3 units per day or ≥4 units per day). Plasma HDL cholesterol concentration, erythrocyte mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT) were determined as indirect biomarkers of alcohol consumption. Sensitivity, specificity, positive and negative predictive value, and proportions of agreement between reported consumption and EtG were calculated. To test the agreement of EtG concentration and alcohol consumption in categories, linear regression analysis was performed. In addition, the association between EtG concentrations and indirect biomarkers was analyzed.ResultsMean age was 53.7 y, and 52.9% of participants men. Of the self-reported abstainers, 92.3% had an EtG concentration <100 ng/mL. Sensitivity was 66.3%, positive predictive value was 96.3%, and negative predictive value was 47.4%. The proportion of positive agreement was 78.5%, and the proportion of negative agreement was 62.7%. EtG concentrations were linearly associated with higher categories of alcohol consumption (P-trend < 0.001), adjusted for age, sex, and renal function. EtG was positively related to MCV, HDL cholesterol, and GGT but not to AST and ALT concentrations.ConclusionsThis study shows that urinary EtG is in reasonable agreement with self-reported alcohol consumption and therefore can be used as an objective marker of habitual alcohol consumption in the general population.

High-intensity interval training has a greater effect on reverse cholesterol transport elements compared with moderate-intensity continuous training in obese male rats.

The present study compares the effect of high-intensity interval training (HIIT; 18 min) and moderate-intensity continuous training (MIT; 1 h) on reverse cholesterol transport (RCT) elements in obese subjects. Thirty adult male rats were induced high-fat diet (HFD) for 12 weeks. After four weeks, the rats were randomly divided into three groups while simultaneously continuing the HFD for the remaining eight weeks. Group specificities were HFD-control, HFD-MIT and HFD-HIIT. The rats were sacrificed 48 h after the last training session and the samples were collected. Analysis of variance and Pearson's correlation test were used for the statistical analyses (significance level: p ≤ 0.05). The results showed that both HIIT and MIT improved heart ABCA1, ABCG1, ABCG4, ABCG5, ABCG8, LXR-α and PPARγ gene expression as well as plasma Apo A1, LCAT, lipids and lipoproteins (p ≤ 0.05). Moreover, higher cardiac ABCA1, ABCG1, ABCG4, ABCG5, ABCG8 and PPARγ expression and plasma high-density lipoprotein cholesterol (p ≤ 0.05) concentrations were found in the HFD-HIIT group compared with the HFD-MIT group. HIIT may have more cardioprotective effects than MIT against atherosclerosis, along with saving time, as supported by the changes observed in the main factors involved in the RCT process.

Inheritance of high and low HDL: mechanisms and management

The inverse association between plasma high-density lipoprotein cholesterol (HDL-C) concentration and the incidence of cardiovascular disease (CVD) has been unequivocally proven by many epidemiological studies. There are several genetic disorders affecting HDL-C plasma levels, either providing atheroprotection or predisposing to premature atherosclerosis. However, up to date, there has not been any pharmacological intervention modulating HDL-C levels, which has been clearly shown to prevent the progression of CVD. Thus, clarifying the exact underlying mechanisms of inheritance of these genetic disorders that affect HDL is a current goal of the research, as key roles of molecular components of HDL metabolism and function can be revealed and become targets for the discovery of novel medications for the prevention and treatment of CVD. Primary genetic disorders of HDL can be either associated with longevity or, in contrast, may lead to premature CVD, causing high morbidity and mortality to their carriers. A large body of recent research has closely examined the genetic disorders of HDL and new promising therapeutic strategies have been developed, which may be proven beneficial in patients predisposed to CVD in the near future. We have reviewed recent findings on the inheritance of genetic disorders associated with high and low HDL-C plasma levels and we have discussed their clinical features, as well as information about new promising HDL-C-targeted therapies that are under clinical trials.

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin's concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = - 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin's secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

Cardiometabolic Risk Factors in Men with Elevated Macroprolactin Content: A Pilot Study.

Macroprolactinemia is a condition associated with the presence of large amounts of high molecular weight complexes of prolactin. Despite high prevalence, clinical significance of macroprolactin remains poorly understood. The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia. The study population included 11 men with isolated macroprolactinemia, 14 subjects with monomeric hyperprolactinemia and 14 men with prolactin levels within the reference range. Glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined in all included patients. Compared to healthy counterparts, men with isolated macroprolactinemia had higher levels of 2-h postchallenge glucose, hsCRP and fibrinogen, lower levels of 25-hydroxyvitamin D and reduced insulin sensitivity. Patients with monomeric hyperprolactinemia were characterized by increased plasma levels of 2-h postchallenge glucose, triglycerides, uric acid, hsCRP, fibrinogen and homocysteine, reduced insulin sensitivity and decreased plasma concentrations of HDL cholesterol and 25-hydroxyvitamin D. Subjects with isolated macroprolactinemia differed from patients with monomeric hyperprolactinemia in postchallenge plasma glucose, insulin sensitivity, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D. In men with monomeric hyperprolactinemia, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D, while in men with elevated levels of macroprolactin, uric acid, hsCRP, fibrinogen and 25-hydroxyvitamin D correlated with a content of monomeric prolactin or macroprolactin, respectively, as well as with a degree of insulin sensitivity. The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia.

Is there a relationship between vitamin D nutritional status and metabolic syndrome in childhood acute lymphoblastic leukemia survivors? A PETALE study

Treatment of childhood acute lymphoblastic leukemia (cALL) has reached unprecedented success leading to survival rates reaching 90%. This is regrettably linked to increased risk of developing long-term health-related sequels into early adulthood. This study aims at assessing the relationship between the vitamin D status and metabolic biomarkers in PETALE, a well-characterized cohort of cALL survivors. We demonstrate that 15.9% of the study participants exhibited 3 or more metabolic syndrome (MetS) risk factors. We also show a direct relationship between s25OHD3 and plasma HDL-Cholesterol concentrations in female but not male participants. Our data, from a metabolically well-described cohort, support a modest role for vitamin D in lipid metabolism in childhood leukemia survivors. The major outcome of this study is the strong association between HDL-Cholesterol concentration and s25OHD3 only in female subjects, thereby conveying vitamin D a gender-specific cardio-protective effect. cALL survivors represent a population at higher risk for secondary diseases. For this reason thorough nutritional evaluation, including vitamin D should be part of the regular follow-up.